Porcine FAD-containing monooxygenase metabolizes lidocaine, bupivacaine and propranolol in vitro

Ru Feng Wu, Cheng Xu Liao, Shuhei Tomita, Yoshiyuki Ichikawa, Lance S. Terada

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Lidocaine, bupivacaine and propranolol are amines that can be expected to act as substrates for FAD-containing monooxygensae (FMO) (EC 1. 14. 13. 8). We found that FMO metabolizes lidocaine, bupivacaine and propranolol. The Km and Vmax values of lidocaine, bupivacaine and propranolol for FMO are 143, 408 and 210 μM, and 145, 119 and 135 nmol/min/mg FMO protein, respectively. The lipophilicity of the drugs decreased in the following order: lidocaine>propranolol>bupivacaine, under our experimental conditions. Furthermore, the metabolic products of FMO were separated by high-performance liquid chromatography and analyzed by gas chromatography-mass spectrometry, and were found to be the N-oxides and N-hydroxylamines of the respective drugs. These findings suggest that lidocaine, bupivacaine and propranolol are substrates for FMO, and the enzymatic toward lidocaine or bupivacaine may be inhibited exclusively and competitively by propranolol.

Original languageEnglish (US)
Pages (from-to)1011-1019
Number of pages9
JournalLife Sciences
Volume75
Issue number8
DOIs
StatePublished - Jul 9 2004

Keywords

  • Bupivacaine
  • FAD-containing monooxygenase
  • Lidocaine
  • Propranolol
  • β-adrenergic-blocking reagent

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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